1. Field of the Invention
The present application relates to a system for designing promoters for efficient expression of genes.
2. General Background and State of the Art
Despite early expectations as a promising new technology for the treatment of various diseases, convincing clinical efficacy of gene therapy has not been demonstrated in most of the trials conducted so far. One of the major technical hurdles in clinical gene therapy has been the difficulty of delivering the therapeutic gene into specific target cells and maintaining transgene expression at a sufficiently high level for a desirable amount of time. Although targeting the delivery of therapeutic genes to specific cell types (targeted transduction) will be the most desirable, it represents a major technical obstacle and only limited success has been reported in this field (5, 24, 48). As an alternative approach, scientists have used cell type-specific promoters to restrict expression of transgenes only in target cells (targeted transcription) (18). These promoters are tailored from genes expressed specifically in the same target cells (28, 43, 51, 55). However, these so-called cell-specific promoters are frequently leaky in terms of target cell selectivity, causing transgene expression in non-target cells at variable levels. In most cases, these promoters are not strong enough to mediate transgene expression at or above the level required for realistic therapeutic effects. These facts indicate a need for a more systemic approach for the development of highly efficient cell type-specific promoter systems.